Paraneoplastic Syndromes in Hepatocellular Carcinoma, Epidemiology, and Survival: A Retrospective Seven Years Study.

Background and Objectives: Liver cancer poses a significant global health threat, ranking among the top three causes of cancer-related deaths. Patients with hepatocellular carcinoma (HCC) often present with symptoms associated with neoplasms or unusual clinical features such as paraneoplastic syndromes (PNS), including hypoglycemia, hypercholesterolemia, thrombocytosis, and erythrocytosis. Our study aimed to investigate the prevalence, clinical characteristics, and survival outcomes associated with PNS in HCC patients and assess each PNS's impact on patient survival. Materials and Methods: We conducted a retrospective analysis of PNS clinical features and survival among consecutive HCC patients diagnosed at our department over seven years, comparing them with HCC patients without PNS. The study involved a retrospective data evaluation from 378 patients diagnosed with HCC between January 2016 and October 2023. Results: We obtained a PNS prevalence of 25.7%, with paraneoplastic hypercholesterolemia at 10.9%, hypoglycemia at 6.9%, erythrocytosis at 4.5%, and thrombocytosis at 3.4%. Patients with PNS tended to be younger and predominantly male. Multivariate analysis revealed a strong correlation between PNS and levels of alpha-fetoprotein and tumor size, with diabetes also showing a significant statistical association (p < 0.05). Subgroup analysis based on specific paraneoplastic syndromes demonstrated shorter survival in patients with PNS, albeit without significant statistical differences, except for hypoglycemia (p < 0.0001). Matched analysis indicated a shorter survival rate for patients with PNS, although no significant statistical differences were observed. Conclusions: PNS are frequently observed in HCC cases and are associated with unfavorable prognoses and decreased survival rates due to their correlation with increased tumor burdens. However, they do not independently predict poor survival. The impact of individual PNS on HCC prognosis varies.

Paraneoplastic syndromes associated with classic Hodgkin lymphoma, a systematic literature review.

PNS are uncommon manifestations of cancer. The current literature about these syndromes in the setting of cHL is disintegrated. A systematic literature review of all published literature was conducted. One hundred twenty-eight patients from 115 publications met the inclusion/exclusion criteria. Eight-five patients were of the NS subtype (66.4%). The most frequent clinical presentation of the PNS was CNS manifestation (25.8%). The majority of patients were diagnosed with the cHL and PNS simultaneously (42.2%). In 33.6% of patients, the lymphoma diagnosis preceded the PNS diagnosis. In 16.4% of patients, the PNS diagnosis preceded the lymphoma diagnosis. The presence of PNS antibodies was reported in 35 patients (27.3%). Age older than 18 was associated with higher prevalence of PNS. The CR rate of the lymphoma was 77.3%. The complete resolution rate of the PNS was 54.7%. Relapse of lymphoma was reported in 13 patients, and recurrence of the PNS upon relapse was reported in 10/13 patients.

Incidence and clinical relevance of paraneoplastic syndromes in patients with renal cell carcinoma.

BACKGROUND: Paraneoplastic syndromes (PNS) are defined as the signs and symptoms attributed to cytokines or hormones released from a tumor or a patient's immune system. PNS have been reported with many cancers for decades and data supporting their relevance in renal cell carcinoma (RCC) are largely historical. The widespread use of electronic medical record (EMR) systems provides a more robust method to capture data. The objective of this study was to establish contemporary data regarding the incidence and relevance of PNS in patients undergoing nephrectomy for suspected RCC. METHODS: In this retrospective single-institution study, 851 patients undergoing nephrectomy for suspected RCC between 2011 and 2018 were assessed for the presence or absence of PNS as defined by laboratory abnormalities. Factors associated with PNS and with all-cause mortality were examined. RESULTS: The incidence of PNS was 33.1% among 851 patients prior to nephrectomy. The most prevalent PNS were anemia (22.4%), thrombocytosis (7.5%), and elevated C-reactive protein (CRP) (7.4%). PNS were more common in women (39.2% vs. 29.4%, p = 0.0032) and higher stage RCC (31.1% of stage I vs. 54.2% of stage IV, p = 0.0036). Factors associated with the presence of PNS in multivariable analysis included female gender, high comorbidity, and stage IV RCC. Prenephrectomy PNS were associated with poorer survival in multivariable analysis (HR: 2.12, p = 0.0002). Resolution of PNS occurred in 52.1% of patients after nephrectomy, including 55.2% with stage I to III and 38.5% with stage IV RCC (p = 0.10). CONCLUSIONS: Using EMR data, laboratory evidence of PNS was present in one-third of a contemporary cohort of patients undergoing nephrectomy, with >50% of PNS resolving after surgery. Consistent with prior reports, PNS are more common in higher-stage RCC and are associated with poorer survival in RCC patients.

Hyperparathyroidism in a Large Cohort of Chinese Patients With Tumor-induced Osteomalacia.

CONTEXT: Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome caused by excessive production of fibroblast growth factor 23 (FGF23) by a tumor. Hyperparathyroidism (HPT) including secondary HPT (SHPT) and tertiary HPT (THPT) in TIO patients, which is believed to be associated with phosphate supplementation, has not been well documented. OBJECTIVES: To clarify the prevalence, clinical characteristics, and risk factors for HPT in a large cohort of Chinese patients with TIO in our hospital. DESIGN, SETTING, AND PARTICIPANTS: This retrospective study enrolled 202 patients with TIO. MAIN OUTCOME MEASUREMENTS: Occurrence of HPT in patients with TIO. RESULTS: HPT was observed in 91 patients (91/202, 45.1%): 84 patients (41.6%) with SHPT and 7 patients (3.5%) with THPT. All patients with THPT underwent parathyroidectomy and only 1 patient experienced recurrence. Compared with patients without HPT, patients with SHPT had longer disease duration, higher rate of phosphate and calcitriol supplementation, lower serum calcium, lower urine calcium excretion, and higher urine phosphate excretion. Compared with patients with SHPT, patients with THPT had even longer disease duration and a higher rate of phosphate and calcitriol supplementation. PTH levels showed positive correlation with intact FGF23 and 1,25-dihydroxyvitamin D levels, but not 25-hydroxy vitamin D level in patients with TIO. Multivariate logistic regression analysis showed that long disease duration and phosphate supplementation were independently associated with occurrence of HPT in patients with TIO. Further logistic regression analysis and restricted cubic spline model revealed dose-response relationship between cumulative dose of phosphate supplementation and PTH levels. CONCLUSIONS: HPT is common in patients with TIO. To avoid the occurrence of HPT in patients with TIO, timely diagnosis and tumor resection is necessary and an excessive dose of phosphate supplementation is not suggested before surgery.

Primary thymus tumors: retrospective case analysis at a reference center in Latin America, 2011-2019.

BACKGROUND: Thymic tumors are unusual neoplasms, representing 0.2 to 1.5% of tumors in humans, but correspond to 20% of mediastinal tumors and 50% of those that occur in the anterior mediastinum. They tend to appear around the fourth and fifth decades of life without gender predilection. Up to 30% of patients are asymptomatic, therefore many are incidentally diagnosed. Radical thymectomy is the treatment of choice with high survival rates when detected in the early stages. METHODS: This was a retrospective descriptive study, including 18 adult patients' diagnosis of thymic neoplasm, who were managed with surgical resection from 2011 to 2019. Information about demographics, clinical characteristics, imaging findings, surgical and medical management, plus histological findings was obtained and reported. RESULTS: 18 patients with thymic tumors were included, of which specific histologic studies reveled thymomas, carcinomas, neuroendocrine tumors, thymolipoma and thymic cyst. Mean age was 52.7 years, with a predominance of male population. The main symptom was dyspnea, followed by cough and chest pain. Paraneoplastic syndromes such as myasthenia gravis, aplastic anemia and Cushing syndrome were reported. 89% of cases were treated by radical thymectomy alone, while only 2 cases required chemotherapy and radiotherapy. There were no surgical complications. Mean hospital stay length was 11. 9 days, with only 1 mortality during hospital admission. 5-year survival rate was 81%. CONCLUSIONS: The treatment of choice is radical thymectomy, which has been shown to positively impact patient mortality. Early detection is key to improve patient outcomes.

Characteristics of hospitalized dermatomyositis patients with underlying malignancy: a nationally representative retrospective cohort study.

INTRODUCTION: Little is known regarding characteristics of hospitalized dermatomyositis (DM) patients. Understanding the unique characteristics of hospitalized DM patients with underlying malignancy is important in guiding development of specific work-up and treatment algorithms. OBJECTIVES: We aim to characterize the inpatient burden of DM patients with malignancy (DM malignancy), determine unique characteristics of DM-malignancy inpatients, and assess trends and predictors of cost of care and length of stay for hospitalized DM-malignancy patients. METHODS: Hospitalized DM patients with and without malignancy were characterized and compared using 2009-2015 National Inpatient Sample. Associated malignancies, risk factors for malignancy, and trends/predictors for cost of care and length of stay were evaluated using multivariable models. RESULTS: Prevalence of malignancies among hospitalized DM inpatients was 10.9%. Age > 40 years and female sex were significantly associated with increased malignancy risk in DM inpatients. Numerous malignancies were significantly more common in men with DM compared to women, including bronchial, non-Hodgkin's lymphoma, head/neck, bladder, esophageal, kidney, and stomach. The most common malignancies in women with DM were breast and ovarian. Head/neck carcinomas were more common in hospitalized DM patients than previous cohorts evaluating outpatients. Socioeconomic characteristics differed between DM patients with/without malignancy. The presence of underlying malignancy did not affect hospitalization cost, length of stay, or mortality in the hospitalized DM population. The economic burden of hospitalized DM patients is increasing over time. CONCLUSIONS: DM inpatients with malignancy display numerous differences compared to DM inpatients without malignancy. Further research characterizing hospitalized DM patients is warranted in order to optimize work-up and treatment guidelines for these patients.

The genetic polymorphisms of XPR1 and SCL34A3 are associated with Fanconi syndrome in Chinese patients of tumor-induced osteomalacia.

PURPOSE: Tumor-induced osteomalacia (TIO) is an acquired form of hypophosphatemia caused by tumors with excess production of fibroblast growth factor 23 (FGF23). Some reports showed that TIO patients had renal Fanconi syndrome (FS) with unidentified mechanism. In this study, we investigated the association between genetic polymorphisms of phosphate transporters in renal proximal tubules and TIO with FS. METHODS: We recruited 30 TIO patients with FS (TIO-FS) as well as 30 TIO patients (TIO-nonFS) without any urine abnormalities matched by age and gender. We collected clinical manifestations and conducted targeted sequencing of SLC34A1, SLC34A3 and XPR1 genes and the association analysis between variants in TIO with FS and phenotypes. RESULTS: TIO-FS group had lower levels of serum phosphate (0.44 ± 0.12 vs. 0.51 ± 0.07 mmol/L, p < 0.05) than TIO-nonFS group. Among the 16 SNPs in SLC34A1, SLC34A3 and XPR1 genes, GG/GC genotypes of rs148196667 in XPR1 and AA/TA genotypes of rs35535797 in SLC34A3 were associated with a reduced susceptibility to have FS. The G allele of rs148196667 in XPR1 decreased the risk of FS. The GGAA haplotype in SLC34A3 and GCT haplotype in XPR1 were associated with a decreased risk for FS. CONCLUSIONS: The polymorphisms of XPR1 and SCL34A3 are associated with TIO patients with Fanconi syndrome. It provides novel insight to the relationship of phosphate transportation and general functions of renal proximal tubules.

Features and Risk Factors for Paraneoplastic Autoimmune Multiorgan Syndrome in 145 Chinese Patients.

Paraneoplastic autoimmune multiorgan syndrome is a complex and deadly disease. We retrospectively reviewed the clinical features and risk factors for paraneoplastic autoimmune multiorgan syndrome in 145 Chinese patients. The most common neoplasm was Castleman disease (56%), and patients with Castleman disease tended to be younger (≤ 42 years old: 83% vs. 29%) and to have a greater proportions of lichen planus-like lesions (47% vs. 27%) and bronchiolitis obliterans (49% vs. 29%), compared to other neoplasm-associated patients. Among all 145 patients in the study, the survival rates were 84% at 1 year, 65% at 3 years, and 54% at 5 years. Kaplan-Meier curve analysis revealed that mortality was associated with older age (> 42 years), neoplasm type, labial lesions, and larger skin lesion area (> 17.5% of the body surface area). However, only older age and larger skin lesion area were independent factors associated with mortality in multivariate analysis. We suggest that patients with Castleman disease and paraneoplastic autoimmune multiorgan syndrome have many unique characteristics and the underlying risk factors for death require further exploration.

Comparing Clinical, Imaging, and Physiological Correlates of Intestinal Pseudo-Obstruction: Systemic Sclerosis vs Amyloidosis and Paraneoplastic Syndrome.

INTRODUCTION: Intestinal pseudo-obstruction is characterized by impaired transit and luminal dilation in the absence of mechanical obstruction. Our study aims to describe the clinical, radiographic, and physiological findings in pseudo-obstruction associated with systemic sclerosis (SSc), amyloidosis, and paraneoplastic syndrome. METHODS: A retrospective cohort of patients evaluated at our institution between January 1, 2008, and August 1, 2018, was assembled. Clinical, imaging, and physiological characteristics were abstracted from electronic medical records. RESULTS: We identified 100 cases of pseudo-obstruction (55 SSc, 27 amyloidosis, and 18 paraneoplastic). Female population predominance was seen in SSc (71%) vs male population in amyloidosis (74%). Most common symptom was abdominal bloating in all 3 groups. Vomiting was more common in SSc than amyloidosis (73% vs 46%, P = 0.02). Diarrhea was more common in amyloidosis and SSc compared with paraneoplastic (81% and 67% vs 28%, P < 0.01). Weight loss (>5%) was more common in SSc compared with amyloidosis and paraneoplastic (78% vs 31% and 17%, P < 0.0001). Only small bowel dilation was seen in 79%, 40%, and 44% and only large bowel dilation in 2%, 44%, and 44% of patients in SSc, amyloidosis, and paraneoplastic, respectively. Five of 8 SSc patients had myopathic and 3 of 5 paraneoplastic had neuropathic involvement on gastroduodenal manometry. DISCUSSION: SSc-associated pseudo-obstruction demonstrates female population predominance and presents with vomiting, diarrhea, and weight loss. Amyloidosis-associated pseudo-obstruction shows male population predominance. Small bowel is more commonly involved than large bowel on both imaging and transit studies in SSc. Myopathic involvement was more common in SSc, contrary to neuropathic in paraneoplastic syndrome.

Patients who report cording after breast cancer surgery are at higher risk of lymphedema: Results from a large prospective screening cohort.

OBJECTIVES: To identify the association between cording and breast cancer-related lymphedema (BCRL); describe time course, location, symptoms and functional impairments. METHODS: A total of 1181 patients were prospectively screened for BCRL after breast cancer (BC) surgery, including patient-reported outcome measures (4193) and perometric arm volume measurements (BCRL defined as relative or weight-adjusted volume change [RVC or WAC] ≥10% ≥3 months postoperatively). RESULTS: A total of 374/1181 patients (31.7%) reported cording first a median of 4.5 months postoperatively, and were more likely to: have body mass index less than 30 kg/m2 ; be less than 55 years of age; have had mastectomy, axillary lymph node dissection, regional lymph node radiation, neoadjuvant chemotherapy (all P < .001), or RVC/WAC ≥10% (P = .002). Patients who reported cording had 2.4 times the odds of developing BCRL compared to those who did not (odds ratio = 2.40; 95% confidence interval = 1.40-4.11; P = .002), and most frequently reported these symptoms: tenderness (61.2%), aching (60.7%), and firmness/tightness (59.8%). On multivariable analysis, cording was significantly correlated with functional difficulty for 17 actions. CONCLUSIONS: Patients frequently present with cording, potentially months after BC surgery. Risk factors for and symptoms of cording are identified, and treatment is recommended. Patients reporting cording are at higher risk of BCRL, therefore, cording should be incorporated into BCRL risk stratification.

Paraneoplastic Syndromes Associated with Laryngeal Cancer.

OBJECTIVES: Paraneoplastic syndromes occur rarely in association with laryngeal cancer. When present, the syndrome may be the first sign of the malignancy. The aim of the present study was to review and report on all published cases in the international literature. METHODS: A search of PubMed was conducted for "paraneoplastic syndromes in laryngeal cancer" without any restrictions on language or publication year. The full texts of all relevant articles were reviewed and all cases of paraneoplastic syndromes associated with any type of laryngeal cancer were extracted and analyzed. RESULTS: We identified 59 cases of paraneoplastic syndromes related to laryngeal cancer in the literature published from 1963 until recently. There were 46 squamous cell carcinomas and 10 neuroendocrine carcinomas. Twenty-two of the paraneoplastic syndromes involved the endocrine system, 21 were dermatologic or cutaneous, 8 neurologic, 5 osteoarticular or rheumatologic, 1 ocular, 1 muscular, and 1 hematologic. Treatment strategies included surgery, radiotherapy, chemotherapy, and often multimodal therapy, depending on the histology and stage of the laryngeal cancer. CONCLUSIONS: Because of their rarity, paraneoplastic syndromes associated with laryngeal cancer are difficult to diagnose. By presenting and systematically reviewing all published cases in the international literature, the present review may help clinicians to recognize them and to suspect the diagnosis of laryngeal cancer at an earlier stage than otherwise might be possible.

Axillary web syndrome among Chilean women with breast cancer: incidence and possible predisposing factors.

PURPOSE: Breast cancer (BC) is the most common cancer in women worldwide. The main treatment for BC is surgery, which involves an axillary procedure that associates with the development of axillary web syndrome (AWS). The incidence of AWS among Chilean women with BC and its possible predisposing factors are currently unknown. Thus, we aimed to (1) determine the incidence of AWS among Chilean women with BC after surgery and (2) identify possible predisposing factors. METHODS: Within 90 days post-surgery, patients were assessed for AWS, i.e., palpable or visible axillary cords in the axillary region extending down from the mid-axilla to the ipsilateral arm. We then computed the odds ratio with 95% confidence interval (OR [95% CI]) for having AWS considering the following predisposing factors: age, body mass index (BMI), number of lymph nodes removed, axillary procedure, days from surgery to the physical therapy assessment, hospital for the surgery, type of breast surgery, and neoadyuvant chemotherapy. RESULTS: AWS was present in 49 out of 107 patients (45.8%). Younger age and lower BMI appeared as the sole predisposing factors for AWS (age, 0.95 [0.91-0.99]; BMI, normal weight 1.00, overweight 0.35 [0.11-1.12], obesity 0.28 [0.08-0.97]). CONCLUSION: The incidence of AWS among Chilean women with BC was 45.8%. Our study also confirms data from previous reports showing that younger age and low BMI are associated with the development of AWS.

Myofascial pain, widespread pressure hypersensitivity, and hyperalgesia in the face, neck, and shoulder regions, in survivors of head and neck cancer.

PURPOSE: Medical treatment for head and neck cancer may induce the presence of inflammation, pain, and dysfunction. The purpose of the current study was to assess the presence of myofascial trigger points (TrPs) and their relationship with widespread pressure hypersensitivity and hyperalgesia in survivors of head and neck cancer (sHNC). METHODS: TrPs and pressure-pain thresholds (PPTs) were quantified in different muscles/joints in the head and neck of 30 sHNC (59.45 ± 13.13 years) and 28 age- and sex-matched controls (58.11 ± 12.67 years). RESULTS: The sHNC had more TrPs in all muscles on the affected side (p < 0.05) than did the healthy controls, and in the temporalis, masseter, and suboccipitalis muscles on the unaffected side (p < 0.05). They also had lower PPTs in all places (p < 0.05) except for the temporalis muscle (p = 0.114) and C5-C6 joint (p = 0.977). The intensity of cervical pain correlated positively with the presence of upper trapezius TrPs. CONCLUSIONS: sHNC suffering cervical and/or temporomandibular joint pain have multiple active TrPs and experience widespread pressure hypersensitivity and hyperalgesia, suggestive of peripheral and central sensitization.

Worsening and newly diagnosed paraneoplastic syndromes following anti-PD-1 or anti-PD-L1 immunotherapies, a descriptive study.

BACKGROUND: Paraneoplastic syndromes (PNS) are autoimmune disorders specifically associated with cancer. There are few data on anti-PD-1 or anti-PD-L1 immunotherapy in patients with a PNS. Our objective was to describe the outcome for patients with a pre-existing or newly diagnosed PNS following the initiation of anti-PD-1 or anti-PD-L1 immunotherapy. METHODS: We included all adult patients (aged ≥18) treated with anti-PD-1 or anti-PD-L1 immunotherapy for a solid tumor, diagnosed with a PNS, and registered in French pharmacovigilance databases. Patients were allocated to cohorts 1 and 2 if the PNS had been diagnosed before vs. after the initiation of immunotherapy, respectively. FINDINGS: Of the 1304 adult patients screened between June 27th, 2014, and January 2nd, 2019, 32 (2.45%) had a PNS and were allocated to either cohort 1 (n = 16) or cohort 2 (n = 16). The median (range) age was 64 (45-88). The tumor types were non-small-cell lung cancer (n = 15, 47%), melanoma (n = 6, 19%), renal carcinoma (n = 3, 9%), and other malignancies (n = 8, 25%). Eleven (34%) patients presented with a neurologic PNS, nine (28%) had a rheumatologic PNS, eight (25%) had a connective tissue PNS, and four (13%) had other types of PNS. The highest severity grade for the PNS was 1-2 in 10 patients (31%) and ≥ 3 in 22 patients (69%). Four patients (13%) died as a result of the progression of a neurologic PNS (encephalitis in three cases, and Lambert-Eaton syndrome in one case). Following the initiation of immunotherapy, the PNS symptoms worsened in eight (50%) of the 16 patients in cohort 1. INTERPRETATION: Our results show that PNSs tend to be worsened or revealed by anti-PD-1 or anti-PD-L1 immunotherapy. Cases of paraneoplastic encephalitis are of notable concern, in view of their severity. When initiating immunotherapy, physicians should carefully monitor patients with a pre-existing PNS.

Paraneoplastic syndromes and oncological outcomes in renal cancer.

BACKGROUND: Paraneoplastic syndromes (PNS) have been defined as a constellation of symptoms and signs seen in patients with malignancy, which cannot be ascribed to the local or distant spread of the tumor. Renal cell carcinoma (RCC) is most commonly associated with PNS among urological malignancies. We describe the incidence of PNS and the association between the syndromes and oncological outcomes in our patients with RCC. SUBJECTS AND METHODS: A retrospective cohort study done at Lagos State University Teaching Hospital, Ikeja, Lagos. This was a retrospective review of our patients who had RCC over 11-year period (2006 to 2016). The incidence of PNS syndromes were hypercalcemia, Stauffer's syndrome, hypertension, anemia, elevated erythrocyte sedimentation rate (ESR), persistent leukocytosis, and its correlation to outcome of disease were analyzed. In addition, the age, gender, clinical features, and stage of disease were analyzed. Chi square, Fischer exact test, and Kaplan-Meier survival, curve and logistic regression. RESULTS: : In total, 101 patients were operated within the period. Age of the patients ranged from 11 to 81 years (mean of 45.17 ± 16.3). There were 46 males and 55 females with M:F ratio of 1:1.2. Majority of the patients, 74 (73%), had clear cell variant of RCC. Twenty-seven patients (26.7%) had triad of flank pain, flank mass, and hematuria. The incidence of PNS were hypercalcaemia 7 (6.9%), Stauffer's syndrome 12 (11.9%), hypertension 16 (15.8%), anemia 61 (60.4%), elevated ESR 56 (55.4%), and persistent leukocytosis 3 (3.0%). At a median follow-up of 6 months, 72 patients (71.3%) were alive, whereas 29 patients (28.7%) were dead. CONCLUSION: Among the PNS, only Stauffer's syndrome was significantly associated with poor outcome.

Recent Updates on the Relationship between Cancer and Autoimmune Pancreatitis.

Autoimmune pancreatitis (AIP) is now considered a pancreatic manifestation of a newly proposed disease condition, IgG4-related disease (IgG4-RD). IgG4-RD is characterized by enhanced IgG4 antibody responses and multiple organ involvements. Recent epidemiological studies have addressed the incidence of cancer in patients with AIP and/or IgG4-RD. Surprisingly, a significant number of AIP patients were detected with cancer at or within one year of the diagnosis of AIP. Furthermore, around 50% of all cancers detected in AIP patients comprised mainly 3 types (gastric, lung, and prostate cancer). Thus, AIP appears to be associated with cancer of other organs rather than the pancreas itself, which suggests that AIP is not a pre-cancerous condition of the pancreas. Moreover, the simultaneous occurrence of cancer and AIP in many patients has led to the establishment of an attractive concept that AIP might sometimes arise from co-existing cancers as a paraneoplastic syndrome.

Endocrine paraneoplastic syndromes in patients with neuroendocrine neoplasms.

OBJECTIVE: Our aim was to assess the prevalence of endocrine paraneoplastic syndromes (EPNS) in neuroendocrine neoplasms (NENs) and estimate its impact on patient outcomes. DESIGN: This is a retrospective analysis of 834 patients with NENs (611 gastrointestinal, 166 thoracic, 57 of unknown and various other primary origin). We included 719 consecutive NEN patients treated at EKPA-Laiko Hospital, Athens, Greece and 115 patients with lung carcinoid (LC) treated at Uppsala University Hospital, Uppsala, Sweden. EPNS diagnosis was based on standard criteria. METHODS: Twenty-one patients with EPNS were detected: 16 with ectopic Cushing's syndrome (ECS), one with hypercalcaemia due to parathyroid hormone-related protein (PTHrP) secretion, three with hypercalcitonaemia and one patient with dual secretion of calcitonin and beta-human chorionic gonadotropin (ß-HCG). All tumours were well-differentiated; 10 patients had Stage IV disease at diagnosis. RESULTS: The prevalence of EPNS in the Greek cohort was 1.9%, whereas that of ECS among LC patients in both centres was 6.7%. Median overall survival (OS) for patients with EPNS was 160.7 months (95%CI, 86-235.4) and median event-free survival (EFS) was 25.9 months (95%CI, 0-57.2). Patients presenting with EPNS prior to NEN diagnosis had longer EFS compared to patients with synchronous or metachronous EPNS (log-rank P = 0.013). Patients with ECS of extra-thoracic origin demonstrated shorter OS and EFS compared to patients with ECS of lung or thymic origin (log-rank P = 0.001 and P < 0.001, respectively). LC patients with and without ECS were comparable in 5-year and 10-year OS rates (66.7% and 33.3% versus 89.8% and 60.2%, respectively; 95%CI [189.6-300.4 months], log-rank P = 0.94) and in median EFS, 67 versus 183 months, 95%CI [50.5-207.5], log-rank P = 0.12). CONCLUSION: EPNS are relatively rare in patients with NENs and mainly concern well-differentiated tumours of the foregut. Among patients with EPNS, LC-related ECS may not adversely affect patient outcomes when diagnosed prior to NEN and effectively been treated.

Thrombosis of the internal jugular vein in the ENT-department - Prevalence, causes and therapy: A retrospective analysis.

OBJECTIVE: Less than 5% of deep vein thrombosis is due to thrombosis of the internal jugular vein. Genetic, malignant or inflammatory underlying diseases as well as insertion of venous catheters can be responsible for this pathology. Due to its rare occurrence, it is difficult to find systematic research about thrombosis of the internal jugular vein. METHODS: We performed a systematic analysis of present patient data from our ENT department with the electronic patient record considering the period from 2012-2017. Search terms were "thrombosis" and "jugular internal vein". We identified 41 patients with the requested diagnosis and performed further analysis of the cases. Internal jugular vein thrombosis was diagnosed in all patients using Duplex sonography and/or CT/MR angiography. RESULTS: Paraneoplastic thrombosis was found in 22/41 patients (54%), in 15 of the 22 (68%), the tumor was located in the ENT region. Two out of seven (29%) of the patients with tumor entities outside the head and neck region had thrombosis of the internal jugular vein as the first symptom of the disease. Another 14/41 patients (34%) had underlying inflammatory diseases - mostly streptococci-associated - for example a cervical abscess. In two patients, insertion of a central-venous catheter was causal, in three patients we could not find any reason for the development of thrombosis. CONCLUSION: To diagnose the rare and often asymptomatic thrombosis of the internal jugular vein, ultrasound of the cervical region should always include vascular imaging. Thrombosis of the internal jugular vein results mostly paraneoplastic or due to inflammation/abscess. It can be the first symptom of a malignant primary disease and always requires detailed diagnostic clarification. LEVEL OF EVIDENCE: 4.

Malignant tumors in autoimmune encephalitis with anti-NMDA receptor antibodies.

OBJECTIVE: The aim of this study was to describe specificities of patients with NMDA receptor antibody (NMDAR-Ab) encephalitis associated with a malignant tumor. METHODS: Retrospective observational study of 252 patients with NMDAR-Ab encephalitis of the French Paraneoplastic Neurological Syndrome Reference Center. Patients were classified in three groups: (1) non-malignant ovarian teratomas, (2) malignant ovarian teratomas (immature), and (3) other malignant tumors. RESULTS: Sixty patients (23.8%) had an associated tumor and 15 (6%) were malignant. No particular neurological symptom was observed in these patients. Ovarian teratomas were the most frequent (51 cases) with 6 of them immature (11.8% of teratomas). Nine patients (3.6%) developed other malignant tumors (3 small cell lung carcinomas, 1 uterine adenocarcinoma, 1 prostate adenocarcinoma, 1 Hodgkin lymphoma, 1 pineal dysgerminoma, 1 neuroblastoma and 1 pancreatic neuroendocrine tumor). Among patients with a cancer other than teratoma, 6/9 were elderly patients (median age 65 years, representing 30% of elderly patients with such encephalitis) compared to a median age of 26 years in adult patients included herein. The clinical course was similar in the three groups, other than a higher death rate among patients with malignant tumors (86 versus 2%; p < 0.001) mainly due to tumor progression (5/7 deaths). CONCLUSION: Immature ovarian teratomas represent 11.8% of all teratomas in patients with NDMAR-Ab encephalitis. The other malignant tumors are mainly observed in elderly patients. The presence of a malignant tumor does not impact the neurological presentation but is directly associated with a higher risk of death.